Previous studies documented the frequent occurrence of severe, progressive malnutrition (PEM) in AIDS and its associations with intestinal dysfunction and with systemic infections. The long term goal of our studies is to provide an understanding of the pathogenesis of malnutrition in AIDS, a scientific rationale for nutritional therapy and realistic expectations for the results of such therapy. The specific aims are to define the characteristic features and pathogenetic mechanisms underlying the alterations in body composition that occur as a result of intestinal diseases with nutrient malabsorption or systemic infections with metabolic alterations, and to design effective strategies for nutritional therapy based upon this knowledge. The scope of the nutritional assessments will be expanded to include precise measurements of body protein, fat and water, plus measurements of energy expenditure and skeletal muscle function. A direct role for the human immunodeficiency virus (HIV) in the pathogenetic process will be sought by correlating its activity with measurements of acute phase reactants, cytokines, inflammatory mediators and metabolic rate. The pathogenesis of fat malabsorption and hypertriglyceridemia will be defined. The effect of treating HIV or other systemic infections upon nutritional status and energy expenditure will be determined. The results of these studies will be incorporated into a series of nutritional treatment studies using enteral and parenteral routes of administration, and evaluating the effects of appetite stimulation. The effects of nutritional therapy upon body composition and upon immunological function will be examined concurrently. These studies should provide a basis for the assessment and therapy of the nutritional complications of AIDS.